title: Lymphocyte proliferation response in patients with delayed hypersensitivity reactions to heparins.
abstract: BACKGROUND
  Heparins can induce delayed-type hypersensitivity (DTH) reactions mediated by specific T lymphocytes. However, the interaction between heparins and lymphocytes has not been sufficiently studied.
  
  
  OBJECTIVE
  To analyse the lymphocyte response to heparins using different types of antigen-presenting cells in patients with DTH reactions to these drugs.
  
  
  METHODS
  We studied seven patients with DTH reactions to heparins diagnosed by delayed reading of intradermal skin testing (n = 5) or drug provocation test (n = 2) and nine tolerant controls. Biopsies were obtained from intradermal testing or during the acute reaction. Peripheral blood mononuclear cells were used to obtain T and B lymphocytes, monocytes and monocyte-derived dendritic cells (DC). T-lymphocyte proliferation was assayed by means of (3)H-thymidine incorporation.
  
  
  RESULTS
  Skin testing showed a high degree of cross-reactivity within low molecular weight heparins with good tolerance to sodium heparin, fondaparinux and lepirudin in most cases. The proliferative response was positive in six patients to most of the heparins tested with both monocytes and B cells (the classical lymphocyte transformation test) or immature DC as antigen-presenting cells, giving a higher response with DC. At a second evaluation 1 year later, the proliferative response was found only with DC, and mainly to the culprit drug.
  
  
  CONCLUSIONS
  A model using DC in the lymphocyte proliferation test is a more appropriate way to assess the immunological response in DTH to heparins; additionally, it can detect a response over a longer time. These findings may be useful for the diagnostic evaluation of drug reactions.
authors.affiliation: Research Laboratory, Carlos Haya Hospital-Fundación IMABIS, 29009 Malaga, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Lopez
authors.forename: M J
authors.initials: MJ
authors.lastname: Torres
authors.forename: R
authors.initials: R
authors.lastname: Rodríguez-Pena
authors.forename: N
authors.initials: N
authors.lastname: Blanca-Lopez
authors.forename: T D
authors.initials: TD
authors.lastname: Fernandez
authors.forename: C
authors.initials: C
authors.lastname: Antunez
authors.forename: G
authors.initials: G
authors.lastname: Canto
authors.forename: V
authors.initials: V
authors.lastname: de Luque
authors.forename: C
authors.initials: C
authors.lastname: Mayorga
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D003429:Cross Reactions; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004334:Drug Administration Schedule; D004342:Drug Hypersensitivity / Q000276:immunology*; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008875:Middle Aged; D012882:Skin Tests
chemical_list: D000925:Anticoagulants; D006493:Heparin